Identification of any publication, patent, or patent application in this section or any section of this application is not an admission that such publication is prior art to the present invention.
Certain diazaspirodecan-2-ones, for example, 8-[{1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one, for example, (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one (the compound of Formula I) are useful antagonists of neuropeptide neurokinin-1 receptors (the “NK-1” receptor antagonists) in the treatment of certain medical conditions, for example, two of the most debilitating side effects of cytotoxic chemotherapy, delayed-phase nausea and vomiting (chemically-induced nausea and emesis, CINE). In therapy utilizing cytotoxic chemotherapy, delayed-phase CINE manifests from between 2 days and 5 days post chemotherapy administration. Acute-phase CINE has been managed by administering a 5HT3 receptor antagonists (e.g., ondansetron), often in combination with a corticosteroid, for example, dexamethasone. This treatment has not been effective in managing delayed-phase CINE. It is believed that acute-phase CINE and delayed-phase CINE arise from different physiological phenomena. It is believed that administration of the NK-1 receptor antagonist of Formula I, or a salt thereof, for example, one or more salts of (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro-[4.5]decan-2-one, either alone or in combination with one or more of a corticosteroid, for example, dexamethasone and/or a 5HT3 receptor antagonist, for example, ondensetron, granisetron, palonosetron, dolasetron, or tropisetron will provide a therapy effective in treatment of CINE in humans.

Synthesis of the compound of Formula I is described in U.S. Pat. No. 7,049,320, issued May 23, 2006 (the '320 patent), U.S. provisional application No. 60/919,666, filed Mar. 22, 2007, and in an international application co-filed in the U.S. receiving office with the present application under Attorney's docket no. CD06628L01US on Mar. 20, 2008, each of which are incorporated herein by reference in their entirety.
Compounds having therapeutic activity must be provided to a patient in a suitable formulation to take advantage of their therapeutic properties. In general, dosage forms suitable for oral administration are preferred. Oral formulations are easy to administer using a non-invasive procedure. Oral dosage forms provide the medicament in a form that is robust in the environment in which it is handled, administered, and stored. Moreover, tablet oral dosage forms conveniently offer the medicament in a variety of discrete dosage sizes and can provide the active pharmaceutical ingredient in a minimum volume per dosage unit. In addition, a tablet can be prepared in fewer unit operations than capsule dosage forms, and tablets, through the provision of tablet “scores”, offer the potential of providing user-selectable multiple dosage strengths using a single dosage unit. Such convenience is unavailable in a capsule dosage form. On the other hand, in many instances, the active pharmaceutical ingredients used in pharmaceutical formulations (API, also termed herein, “drug substance”), especially those having a crystalline form, are not by themselves suitable for forming into a tablet, especially a tablet formed using direct compression techniques. To enable formation of a tablet which can be handled and stored without breakage or loss of material from the tablet (that is, a tablet having low percentage friability), the drug substance must be combined with excipients in a formulation that enables formation of a tablet that is sufficiently robust to withstand handling and storage until the point of use. Moreover, once formed into a tablet, the tableted formulation must be capable of readily releasing the API at a desired point within the gastrointestinal tract when administered to an end user.